The present invention relates generally to the treatment of cancer with chemotherapeutic agents and more specifically to enhancing their effect.
In co-pending application Ser. No. 08/271,902 now U.S. Pat. No. 5,814,295 disclosed are therapeutic agents effective in mitigating tumor progression which agents include a carrier and lymphocyte cells that have been produced by mitogenically stimulating patient excised lymph nodes enriched in tumor-specific lymphocytes enriched in tumor reactive cells, e.g., CD.sub.4 + tumor specific lymphocytes. Lymph nodes enriched in tumor-specific lymphocytes comprising CD.sub.4 + tumor specific lymphocytes were determined by administering a radiolabeled locator to a patient, surgically accessing the patient and locating such lymph nodes with a hand-held radiation detector, and removing the nodes that visually do not contain evidence of tumor. These lymph node lymphocytes are cultured under mitogenic conditions to form the therapeutic agents of interest.
Based on the response reported in patient 4 in application Ser. No. 08/271,902 now U.S. Pat. No. 5,814,295 the inventors stated that subjecting the patients that have received the therapeutic agent of that invention to adjuvant chemotherapy may be of particular benefit to the patient; even to those patients that were recalcitrant to chemotherapy prior to receiving the inventive adoptive cellular therapy treatment disclosed therein. This is particularly important in view of the National Institutes of Health (NIH) consensus report concerning the administration of adjuvant chemotherapy to appropriately staged patients. "NIH Consensus Conference: Adjuvant Therapy for Patients with Colon and Rectal Cancer", JAMA, 1990; 264:1444-50.
In view of the reported findings cited above, the effects of soluble products secreted by the tumor-reactivated lymphocytes expanded from patients with an adenocarcinoma (colorectal cancer) on the chemosensitivity of colorectal tumor cells in vitro were examined in greater depth. The results of these studies is the basis for the present invention.